Cell-type Dependent Alzheimer's Disease Phenotypes: Probing the Biology of Selective Neuronal Vulnerability
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1-s2.0-S2213671117304708-main.pdf
Description
Published version
Size
4.1 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Muratore, Christina R.
Zhou, Constance
Liao, Meichen
Fernandez, Marty A.
Taylor, Walter M.
Lagomarsino, Valentina N.
Pearse, Richard V. II
Rice, Heather C.
Negri, Joseph M.
He, Amy
Date Issued
November 2017
Journal
Stem Cell Reports
Publisher
Elsevier BV
Citation
Muratore, Christina R., et al. “Cell-Type Dependent Alzheimer’s Disease Phenotypes: Probing the Biology of Selective Neuronal Vulnerability.” Stem Cell Reports, 9, 6 (December 2017): 1868–84. © 2017 The Authors
Version
Final published version
Abstract
Authors Alzheimer's disease (AD) induces memory and cognitive impairment in the absence of motor and sensory deficits during its early and middle course. A major unresolved question is the basis for this selective neuronal vulnerability. Aβ which plays a central role in AD pathogenesis, is generated throughout the brain, yet some regions outside of the limbic and cerebral cortices are relatively spared from Aβ plaque deposition and synapse loss. Here, we examine neurons derived from iPSCs of patients harboring an amyloid precursor protein mutation to quantify AD-relevant phenotypes following directed differentiation to rostral fates of the brain (vulnerable) and caudal fates (relatively spared) in AD. We find that both the generation of Aβ and the responsiveness of TAU to Aβ are affected by neuronal cell type, with rostral neurons being more sensitive than caudal neurons. Thus, cell-autonomous factors may in part dictate the pattern of selective regional vulnerability in human neurons in AD. In this article, Muratore et al. examine differential vulnerability of neuronal subtypes in AD by directing iPSC lines from control and familial AD subjects to different regional neuronal fates. APP processing and TAU proteostasis are differentially affected between regional fates, such that neuronal cell type dictates generation of and responsiveness to Aβ.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.STEMCR.2017.10.015
